The proposed continuation application is designed to maximally put into effect the research capabilities of Ponce School of Medicine's senior and recently acquired junior faculty. During the last three years of the MBRS program PSM has dramatically changed from a teaching institution to a research oriented center. The major goals of our MBRS program for last budget period has been achieved, i.e., the research activities have prospered and expanded under MBRS resulting in: a) a wide spectrum of scientific endeavor covering the areas of pharmacology, biochemistry, physiology, immunology, microbiology and environmental toxicology, b) capacity to compete for other external funding through R01's and R29's, c) obtaining basic and necessary equipment for infrastructure, d) obtaining full accreditation of our new Ph.D. in Biomedical Sciences. In addition to the former senior faculty research projects of Dr. J. Torres "Chaperonins from Chromatium Vinosum", Dr. H. Mass "Magnesium Sulfate and Stunned Myocardium", Dr. J. Puig "Isolation and Purification of Morphine UDP-Glucuronosyltransferases", Dr. Montealegre "Purification and Immunodiagnostic Antigens of F. Hepatica", Dr. C. Mercado "Elucidation of the Molecular Mechanism for the Effects of Nitrofurans on CHO and T Cells", Dr. T. Frazer "Epidemiology of IDDM in Puerto Ricans: Genetic Determinants and Family Studies", Dr. E. Eylar "Immune Aging: T Cell Subsets and Transcriptional Regulation", we have included a new series of high quality projects from the new faculty which are as follows: Dr. D. Fitzovich who aims to quantitatively evaluate cardiac, coronary arterial and peripheral vascular function and the mechanisms by which they are controlled in a model of insulin-insensitive obesity in the dog and to assess this preparation's suitability as a model of complications of Type II diabetes mellitus; Dr. S. Yano who proposes to evaluate the roles of lung metallothioneins as. free radical scavengers and lipid peroxidation inhibitors; Dr. Y. Shen who proposes to determine, by PCR, how frequently a peripheral blood monocyte and dendritic cells (DC) from a HIV-1 (+) homosexual males, intravenous drug users (IVDU's) and heterosexual females, virus infected. Dr. J. Matta who aims to study the mechanisms regulating the oxygen-activation/induction of superoxide dismutases and Dr. K. Manoharan who aims to establish a good in vitro mammary transformation model which would be useful to delineate the different stages and mechanisms involved in the transformation process and also to screen specific chemopreventive agents for mammary cancer. Our goals during the next four-years are: 1) set up a faculty and student seminar once a month so that all persons know what each one is doing, 2)promote more collaboration between MBRS researchers so that we have more interaction between departments, 3) enhance enthusiasm among MBRS researchers to submit grant proposals outside of the minority programs, 4) continue an atmosphere of research excellence so that it meets MBRS mission, 5) enhance minority undergraduate and graduate student participation in biomedical research.